T cell receptor-major histocompatibility complex interaction strength defines trafficking and CD103+ memory status of CD8 T cells in the brain
journal contributionposted on 2020-09-14, 10:06 authored by A Sanecka, N Yoshida, EM Kolawole, H Patel, BD Evavold, EM Frickel
T cell receptor-major histocompatibility complex (TCR-MHC) affinities span a wide range in a polyclonal T cell response, yet it is undefined how affinity shapes long-term properties of CD8 T cells during chronic infection with persistent antigen. Here, we investigate how the affinity of the TCR-MHC interaction shapes the phenotype of memory CD8 T cells in the chronically Toxoplasma gondii-infected brain. We employed CD8 T cells from three lines of transnuclear (TN) mice that harbor in their endogenous loci different T cell receptors specific for the same Toxoplasma antigenic epitope ROP7. The three TN CD8 T cell clones span a wide range of affinities to MHCI-ROP7. These three CD8 T cell clones have a distinct and fixed hierarchy in terms of effector function in response to the antigen measured as proliferation capacity, trafficking, T cell maintenance, and memory formation. In particular, the T cell clone of lowest affinity does not home to the brain. The two higher affinity T cell clones show differences in establishing resident-like memory populations (CD103+) in the brain with the higher affinity clone persisting longer in the host during chronic infection. Transcriptional profiling of naïve and activated ROP7-specific CD8 T cells revealed that Klf2 encoding a transcription factor that is known to be a negative marker for T cell trafficking is upregulated in the activated lowest affinity ROP7 clone. Our data thus suggest that TCR-MHC affinity dictates memory CD8 T cell fate at the site of infection.
CD8 T cellsROP7T cell receptor–major histocompatibility complex interactionToxoplasma gondiineurological infection and inflammationAdoptive TransferAnimalsAntigens, CDAntigens, ProtozoanBiomarkersBrainCD8-Positive T-LymphocytesCalciumFlow CytometryHigh-Throughput Nucleotide SequencingImmunologic MemoryImmunophenotypingIntegrin alpha ChainsLymphocyte ActivationMajor Histocompatibility ComplexMiceProtozoan ProteinsReceptors, Antigen, T-CellFrickel FC001076CBBRF-ackFC-ack1107 Immunology